D-mannose alleviates chronic periodontitis in rats by regulating the functions of neutrophils

Abstract Background Periodontitis is a chronic inflammatory disease without effective treatment. Nowadays, the critical role of neutrophils in periodontitis is getting better and better understood. The study aimed to explore the protective effects of D-mannose on chronic periodontitis and determine whether its underlying mechanisms is related to neutrophils. Methods To explore the protective effects of D-mannose on chronic periodontitis, the rat model of lipopolysaccharide (LPS)-induced periodontitis was established, followed by D-mannose treatment by oral gavage. To evaluate the protective effects of D-mannose against periodontal bone loss, methylene blue staining, hematoxylin and eosin (H&E) staining, and micro-CT scanning were utilized. Then, immunofluorescence (IF), Western Blot, and RT-PCR were applied to assess the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-17), anti-inflammatory cytokine (IL-10), tumor necrosis factor-alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), ten-eleven translocation 2 (TET2), and key glycolytic enzymes (HK1, HK2, PFKFB3), and to examine D-mannose's impact on the recruitment and activation of neutrophils in the gingiva. Additionally, neutrophils isolated from the peripheral blood of healthy rats were treated with LPS and D-mannose, and changes in the expression levels of myeloperoxidase (MPO), IL-1β, IL-6, IL-17, IL-10, and TET2 were observed via IF. Results In vivo, D-mannose inhibited LPS-induced alveolar bone resorption in rats and suppressed the expression levels of IL-1β, IL-6, IL-17, TNF-α, G-CSF, GM-CSF, TET2, HK1, HK2, and PFKFB3, upregulated the expression level of IL-10, and inhibited the recruitment and activation of neutrophils in LPS-treated rat gingival tissues. In vitro, D-mannose was found to inhibit the activation of neutrophils stimulated by LPS, downregulate the expression of IL-1β, IL-6, IL-17, and TET2, and upregulate the expression of IL-10. Conclusions D-mannose can alleviate chronic periodontitis in rats by regulating the functions of neutrophils, potentially associated with the expression of TET2 and glycolysis, providing new insights into the potential application of D-mannose to chronic periodontitis.